In Vitro Virology

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Core C: Virology will support Research Projects I, II and III and Cores B and D through the provision of specific reagents, antiviral and other anti-infective evaluations, and efficacy data for the pyrimidinediones, ISIS 5320 oligonucleotide, and NCp7 viral inactivating agents alone and in combination products. Core C will accomplish these goals by implementation of the following objectives: Objective 1: Primary Antiviral Efficacy and Toxicity Testing: The antiviral efficacy and toxicity data will utilize whole virus replication assays and specific cellular and biochemical assays to measure the antiviral effects of the active microbicide and formulated product based on their defined mechanisms of action. Toxicity evaluations will be performed in parallel for each antiviral measurement. Objective 2: Evaluation of the Activity of Combination Microbicide Products: The aim of this objective is to utilize standard in vitro microbicide efficacy assays to evaluate, quantify and prioritize combinations of microbicide products to be developed as long-lasting microbicides for evaluation in ex vivo cervical explant models as well as for further development as gel and ring products. Objective 3: Evaluation of the Effects of Vaginal and Seminal Fluids on Viral Infectivity and Microbicide Efficacy and Toxicity: We will perform in vitro efficacy and toxicity evaluations using seminal plasma and vaginal fluid additives to each of the antiviral assays performed and to further define the biological properties of these fluids on viral infectivity, microbicide action, and cellular toxicity.Objective 4: Development of Microbicide-Resistant Virus Strains and Evaluation of the Ability of the Microbicides to Inhibit the Transmission of Wild Type and Resistant Virus: We will select for viruses that are resistant to each of the microbicides alone and in combination with one another and evaluate the ability of the microbicides to totally suppress the transmission of wild type and resistant viruses.Objective 5: Toxicity Evaluation of Microbicide Products and Formulated Materials: Cell-based in vitro toxicology testing will be performed utilizing cell lines, relevant Lactobacilli species, and ex vivo tissues. Objective 6: Preclinical Development of Microbicide Products Alone and In Combination: Lead microbicide products defined by the studies will be assessed for their antiviral potential consistent with their advancement to clinical testing.